Melinda Varney, PhD.

 

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Melinda Varney, PhD Research Instructor

During my graduate and postdoctoral careers, I developed expertise in my field by extensively studying hematopoietic stem and progenitor cell biology. I have contributed to establishing how specific genetic, dietary, and therapeutic factors influence hematopoiesis and subsequent downstream immune functions. Long-term hematopoietic stem cells are responsible for giving rise to the cells that comprise our immune systems on a daily basis. Proper care must be taken to avoid unnecessary damage to these cells that drive the production of myeloid and lymphoid immune cells throughout our lives. During the course of my career, I have sought to understand the mechanisms by which the process of hematopoiesis is influenced, including how this process may go awry. It is well established that infection affects hematopoiesis as hematopoietic stem and progenitor cells (HSPCs) directly respond to infection through toll-like receptors and indirectly respond to infection by signals from the host that the body needs to replenish immune cells. Though advancement of knowledge in the scientific community has pointed to a necessary balance of eliciting enough HSPC response to fight infection, but not so much that HSPC expansion and active cycling leads to bone marrow and blood malignancies, no group to my knowledge has studied how HSPCs respond to vaccination, both initially after immunization and upon future pathogen interaction in vaccinated hosts.

The long-term objective of my research is to elucidate how vaccine composition and host-pathogen interactions contribute to and are affected by the biology of HSPCs. My proposed strategy for initial studies includes utilizing Bordetella pertussis vaccination and challenge in various mouse models. Since an alteration in vaccination strategy occurred in the 1990s, whooping cough (pertussis) has resurged. This, taken together with the ability of B. pertussis to elicit diverse hematopoietic immune responses in a host, dependent on the composition of vaccine that host has been exposed to, presents an ideal model for the study of hematopoiesis in the context of improved vaccine development. Preliminary data acquired with the help of a skilled team points to an important role for the biological changes that HSPCs undergo upon vaccination in regulating immune response to future pathogen interaction. It is my goal to determine how HSPC biology contributes to vaccine efficacy and what this may indicate for the design of future vaccines as well as the enhancement of current vaccines. Though initial work primarily involves B. pertussis as a model, it is likely that this work will translate to other vaccination models as well. These efforts create an opportunity to influence future vaccine development in a way that is cognizant of balancing level and type of immune responses to pathogen with proper care to preserve health of long term hematopoietic stem cells. Detailed below is a schematic to illustrate the very basics of this concept.